[LbOr15] Hepatic safety of nevirapine: results of the Boehringer Ingelheim Viramune® Hepatic Safety Project

14th International AIDS Conference

Barcelona, Spain — July 7-12, 2002

[TITLE:] Hepatic safety of nevirapine: results of the Boehringer Ingelheim Viramune® Hepatic Safety Project

[AUTHOR(S):] Stern J, Lanes S, Love J, Robinson P, Imperiale M, Mayers D¹

Int Conf AIDS. 2002 Jul 7-12;14:Abstract No. LbOr15

BACKGROUND: The relationship between drug-induced elevations in ALT/AST levels and subsequent significant clinical liver injury is variable and often unpredictable. All ARV classes have been associated with asymptomatic ALT/AST elevations as well as severe, and at times life threatening, clinical liver toxicity.

METHODS: Boehringer Ingelheim (BI) has recently completed the Viramune® Hepatic Safety Project; its primary objective was to identify risk factors for ARV hepatotoxicity. Data from 1,731 nevirapine (NVP)-treated patients and 1,912 control patients who took part in BI-controlled clinical trials, as well as 814 NVP-treated patients in uncontrolled trials, were analyzed. Several observational cohorts (N = 7894) were analyzed to identify risk factors and will be discussed.

RESULTS: Baseline elevations in ALT/AST >2.5xULN, often a surrogate for HCV/HBV co-infection, and baseline CD4 cell counts >350 cells/mm³ were risk factors for both symptomatic and asymptomatic NVP-associated hepatotoxicity. Female gender at higher CD4 counts may be a risk factor. Fulminant hepatitis was rare in clinical trials and not observed in the cohort studies. In controlled clinical trials there was no excess hepatic mortality for NVP compared to controls. Clinical (symptomatic) hepatotoxicity was an infrequent event (rate in BI trials: 1-5%), and usually reversible with NVP discontinuation. The majority of clinical hepatic events occurred in the first 4 - 6 weeks of NVP therapy. Asymptomatic ALT/AST > 5xULN occurred in 0.5-9% of patients in BI trials.

CONCLUSIONS: The majority of NVP-associated hepatic events are asymptomatic and easily addressed by NVP interruption until the ALT/AST return to baseline with subsequent reintroduction of NVP on a case-by case-basis. In cohort studies, NVP was not associated with a greater risk of clinical hepatitis than other ARVs. Guidelines for managing NVP-associated hepatotoxicity will be presented.

Presenting author: Douglas Mayers

1Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, United States.

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